Role of the ENTH Domain in Phosphatidylinositol-4,5-Bisphosphate Binding and Endocytosis
Abstract
Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH 2 -terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys 76 → Ala 76 , with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P 2 is essential for endocytosis mediated by clathrin-coated pits.
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The NH2 terminus of PICALM contains an epsin NH2-terminal homology domain for phosphatidylinositol-4,5-bisphosphate binding, which allows PICALM to sense membrane curvature and regulate the size of clathrin-coated vesicles.
“The NH2 terminus of PICALM contains an epsin NH2terminal homology domain for phosphatidylinositol-4,5bisphosphate binding, which allows PICALM to sense membrane curvature (284) and regulate the size of clathrincoated vesicles (409).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [284]
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- Authors
- Itoh, T., Koshiba, S., Kigawa, T., Kikuchi, A., Yokoyama, S., & Takenawa, T.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- RIKEN (JP)
- SPring-8 (JP)
- Hiroshima University (JP)
- Corresponding author
- Takenawa, Tadaomi
- Venue
- Science
- Published
- 2001-02-09
- Volume
- 291
- Issue
- 5506
- Pages
- 1047-1051
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1977951612
- Cited by
- 469
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 17 · 2019: 7 · 2018: 16 · 2017: 8 · 2016: 14 · 2015: 8 · 2014: 13 · 2013: 18 · 2012: 21
- FWCI
- 18.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- ENTH domain, epsin, phosphatidylinositol 4,5-bisphosphate, clathrin-mediated endocytosis, phosphoinositide binding, AP180, HIP1R, coated pits, protein-protein interaction
- MeSH terms
- Animals, Carrier Proteins, Chlorocebus aethiops, Clathrin, Coated Pits, Cell-Membrane, DNA-Binding Proteins, Endocytosis, Epidermal Growth Factor, Inositol Phosphates, Liposomes, Models, Molecular, Neuropeptides, Protein Conformation, Recombinant Fusion Proteins, Transcription Factors, Zinc Fingers, Protein Structure, Secondary, Protein Structure, Tertiary, Phosphatidylinositol 4,5-Diphosphate, COS Cells, Nuclear Magnetic Resonance, Biomolecular, Amino Acid Substitution, Amino Acid Motifs, Vesicular Transport Proteins, Adaptor Proteins, Vesicular Transport
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